This proposal aims to develop a polymer hydrogel strategy that can be used to improve the clinical care of patients receiving brachytherapy for gynecological cancers. The biocompatible hydrogel will form in situ after being injected into the vaginal space, and later removed by instillation of water to soften the hydrogel for easy extraction. This Phase I proposal focuses on optimizing the polymer hydrogel strategy using clinically relevant reagent volumes to deliver a product ready for preclinical and clinical testing. The hydrogel will serve as vaginal packing material during cervical cancer brachytherapy, displacing rectum and bladder, providing attenuation and stabilizing the applicator. Current alternatives include packing the vagina with gauze, which is uncomfortable for patients, subject to errors and provides limited attenuation of radiation dose, and a commercially available balloon system that is expensive and cumbersome to use. The proposed polymer hydrogel strategy would provide a simple, customized strategy for vaginal packing that provides attenuation and consistent imaging properties while improving patient comfort and limiting costs. Our team has also developed a rigid, reusable, 5-channel vaginal cylinder brachytherapy applicator to be used in conjunction with the hydrogel for vaginal cuff brachytherapy. This improves upon existing options for vaginal cuff brachytherapy by providing a customized solution that conforms to patient anatomy and offers more precise radiation delivery while maintaining an efficient workflow. The small business and academic partners will work together to translate this polymer hydrogel prototype to a clinical product that is readily commercializable. The proposed research in phase I will focus on (Aim 1) optimization of the hydrogel for use as vaginal packing for brachytherapy and on (Aim 2) preclinical validation of hydrogel application and removal in the presence of brachytherapy applicators in a model system designed to simulate clinical conditions. The phase I research will provide the foundation for a phase II program focusing on establishing safety and biocompatibility of the hydrogel for human testing and designing clinical trials to evaluate clinical application of the polymer hydrogel product.